Cancer Research and Treatment

Volume 38(3); June 2006

Original Articles

A Pilot Study of Cisplatin, Irinotecan, Leucovorin and 5-fluorouracil (PILF) Combination Chemotherapy for Advanced Gastric Cancer: Se Hoon Park, Soo Yeon Jeon, Kwang Il Ko, Eunmi Nam, Soo-Mee Bang, Eun Kyung Cho, Dong Bok Shin, Jae Hoon Lee, Woon Ki Lee, Min Chung; Cancer Res Treat. 2006;38(3):121-125. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.121

Purpose

Irinotecan, in combination with leucovorin/5-fluorouracil (FU) or with cisplatin, is known to be active for treating advanced gastric cancer (AGC). This pilot study evaluated a novel three-drug combination of irinotecan, leucovorin/FU and cisplatin as a first-line treatment of AGC. The primary endpoint was to assess the feasibility in anticipation of conducting a larger phase II study.

Materials and Methods

Chemotherapy-naive AGC patients received irinotecan 150 mg/m² on day 1, and leucovorin 200 mg/m² and a 22-h infusion of FU 1000 mg/m² on days 1 and 2. Cisplatin 30 mg/m² was administered on day 2. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity.

Results

Of the 17 eligible patients, two patients had an ECOG performance status of 2 and their median age was 48 years (range: 31 to 69). A total of 117 chemotherapy cycles were delivered (median: 6, range: 1 to 12). The causes of treatment discontinuation were disease progression in 9 patients (53%), refusal (35%) and toxicity (12%). Although grade 3 or 4 neutropenia (41% of patients) was the major toxicity that required dose adjustments, only one episode of febrile neutropenia occurred. Grade 3 or 4 nausea and vomiting, diarrhea and fatigue were observed in 35%, 35% and 29% of patients, respectively. None of the patients died of toxicity during treatment. Of the 16 patients who were evaluable for response, 7 (44%) experienced a partial response.

Conclusion

This novel multi-drug combination was tolerated well in patients with AGC. Based on the encouraging efficacy and tolerability, a randomized phase II study is ongoing in this disease setting.

Citations

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Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric cancer
S.H. Park, E. Nam, J. Park, E.K. Cho, D.B. Shin, J.H. Lee, W.K. Lee, M. Chung, S.I. Lee
Annals of Oncology.2008; 19(4): 729. CrossRef

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Effects of the Expression of Leptin and Leptin Receptor (OBR) on the Prognosis of Early-stage Breast Cancers: Yongnam Kim, Si-Young Kim, Jae Jin Lee, Jeongho Seo, Youn-Wha Kim, Suck Hwan Koh, Hwi-Joong Yoon, Kyung Sam Cho; Cancer Res Treat. 2006;38(3):126-132. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.126

Abstract PDF PubReader ePub

Purpose

Obesity-related leptin and leptin receptor (OBR) have a relation to the development of cancer and metastasis and also the low survival rate for breast cancer patients. Leptin has been associated with increased aromatase activity and it displays functional cross-talk with estrogen. This study was designed to determine the relationship between the expression of leptin and OBR in breast cancer tissue and the prognosis of early-stage breast cancer patients, and especially for the tamoxifen-treated patients.

Materials and Methods

Ninety-five patients with early-stage breast cancer and who had undergone surgical treatment at Kyung Hee University Hospital between January 1994 and June 2004 were analyzed. The surgical specimens underwent immunohistochemical analysis for leptin and OBR. The patients' survival and clinical characteristics were obtained from the medical records.

Results

Of the 95 patients, 79 (83%) and 32 (33.7%) showed the expression of leptin and OBR in breast cancer tissue, respectively. The expression of leptin and OBR in breast cancer tissue was not significantly related to the clinicopathological characteristics, including obesity, the expression of hormonal receptor, the HER-2/neu expression, menopause, stage and the nuclear grade. The expression of leptin and OBR was not significantly related to the overall disease-free survival (DFS). For the tamoxifen-treated postmenopausal obese patients, the DFS of the leptin-positive group was higher than that of the leptin-negative group (p=0.017).

Conclusion

The expression of leptin and OBR in breast cancer tissue may be not a prognostic factor for disease-free survival of breast cancer patients. In the future, further studies are needed to determine whether leptin expression could be a predictive factor for tamoxifen therapy in the postmenopausal obese subgroup among the early breast cancer patients.

Citations

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Exploring the multifaceted role of obesity in breast cancer progression
Sooraj Kakkat, Prabhat Suman, Elba A. Turbat- Herrera, Seema Singh, Debanjan Chakroborty, Chandrani Sarkar
Frontiers in Cell and Developmental Biology.2024;[Epub] CrossRef
Greater Body Fatness Is Associated With Higher Protein Expression of LEPR in Breast Tumor Tissues: A Cross-Sectional Analysis in the Women’s Circle of Health Study
Adana A.M. Llanos, John B. Aremu, Ting-Yuan David Cheng, Wenjin Chen, Marina A. Chekmareva, Elizabeth M. Cespedes Feliciano, Bo Qin, Yong Lin, Coral Omene, Thaer Khoury, Chi-Chen Hong, Song Yao, Christine B. Ambrosone, Elisa V. Bandera, Kitaw Demissie
Frontiers in Endocrinology.2022;[Epub] CrossRef
Association of Serum Leptin with Prognostic Factors in Breast Cancer
Amirreza Hajati, Farshad Talebian, Asrin Babahajian, Nasrin Daneshkhah, Bayazid Ghaderi
Sudan Journal of Medical Sciences.2022; 17(1): 4. CrossRef
Roles and mechanisms of adipokines in drug resistance of tumor cells
Yan Li, Chunyan Yu, Weimin Deng
European Journal of Pharmacology.2021; 899: 174019. CrossRef
Immunohistochemical analysis of adipokine and adipokine receptor expression in the breast tumor microenvironment: associations of lower leptin receptor expression with estrogen receptor-negative status and triple-negative subtype
Adana A. M. Llanos, Yong Lin, Wenjin Chen, Song Yao, Jorden Norin, Marina A. Chekmareva, Coral Omene, Lei Cong, Angela R. Omilian, Thaer Khoury, Chi-Chen Hong, Shridar Ganesan, David J. Foran, Michael Higgins, Christine B. Ambrosone, Elisa V. Bandera, Kit
Breast Cancer Research.2020;[Epub] CrossRef
Leptin signaling axis specifically associates with clinical prognosis and is multifunctional in regulating cancer progression
Tsung-Chieh Lin, Kuan-Wei Huang, Chia-Wei Liu, Yu-Chan Chang, Wei-Ming Lin, Tse-Yen Yang, Michael Hsiao
Oncotarget.2018; 9(24): 17210. CrossRef
Immunohistochemical staining of leptin is associated with grade, stage, lymph node involvement, recurrence, and hormone receptor phenotypes in breast cancer
Mohamad Nidal Khabaz, Amer Abdelrahman, Nadeem Butt, Lila Damnhory, Mohamed Elshal, Alia M. Aldahlawi, Swsan Ashoor, Basim Al-Maghrabi, Pauline Dobson, Barry Brown, Kaltoom Al-Sakkaf, Mohmmad Al-Qahtani, Jaudah Al-Maghrabi
BMC Women's Health.2017;[Epub] CrossRef
Leptin, adipocytes and breast cancer: Focus on inflammation and anti-tumor immunity
Laetitia Delort, Adrien Rossary, Marie-Chantal Farges, Marie-Paule Vasson, Florence Caldefie-Chézet
Life Sciences.2015; 140: 37. CrossRef
Leptine : implication dans la physiopathologie du cancer du sein
Florence Caldefie-Chézet, Virginie Dubois, Laetitia Delort, Adrien Rossary, Marie-Paule Vasson
Annales d'Endocrinologie.2013; 74(2): 90. CrossRef
Serum leptin level and waist-to-hip ratio (WHR) predict the overall survival of metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs)
Mehmet Artac, Hakan Bozcuk, Aysel Kıyıcı, Orhan Onder Eren, Melih Cem Boruban, Mustafa Ozdogan
Breast Cancer.2013; 20(2): 174. CrossRef
Leptin attenuates the anti-estrogen effect of tamoxifen in breast cancer
Xiaofeng Chen, Xiaoming Zha, Wei Chen, Tingting Zhu, Jinrong Qiu, Oluf Dimitri Røe, Jun Li, Zhaoxia Wang, Yongmei Yin
Biomedicine & Pharmacotherapy.2013; 67(1): 22. CrossRef
The role of leptin receptor gene polymorphisms in determining the susceptibility and prognosis of NSCLC in Chinese patients
Yuliang Li, Jianli Geng, Yongzheng Wang, Qinghua Lu, Yimeng Du, Wujie Wang, Zheng Li
Journal of Cancer Research and Clinical Oncology.2012; 138(2): 311. CrossRef
Leptin and breast cancer: an overview
Mehmet Artac, Kadri Altundag
Medical Oncology.2012; 29(3): 1510. CrossRef

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Patterns of Failure after Postoperative Radiation Therapy for Endometrial Carcinoma: Suzy Kim, Hong-Gyun Wu, Hyo-Pyo Lee, Soon-Beom Kang, Yong-Sang Song, Noh-Hyun Park, Sung Whan Ha; Cancer Res Treat. 2006;38(3):133-138. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.133

Abstract PDF PubReader ePub

Purpose

We tried to investigate the outcome and patterns of failure of endometrial cancer patients who were treated with surgery and postoperative radiation therapy (RT).

Materials and Methods

Eighty-three patients with endometrial cancer who received postoperative RT between May 1979 and August 2000 were included in this retrospective study. Forty-one patients received total abdominal hysterectomy, 41 patients received Wertheim's operation and 1 underwent vaginal hysterectomy. Pelvic lymph node dissection or pelvic lymph node sampling was done in 56 patients and peritoneal cytology was done in 35. All the patients were staged according to 1988 FIGO (International Federation of Gynecology and Obstetrics) staging system; 2 were stage IA, 23 were stage IB, 20 were stage IC, 4 were stage IIA, 5 were stage IIB, 9 were stage IIIA, 2 were stage IIIB and 18 were stage IIIC. The histologic diagnoses were adenocarcinoma in seventy-four patients (89%). The histologic grades were Grade 1, 2 and 3 in 21 (25%), 43 (52%) and 10 (12%) patients, respectively. All the patients received external beam RT (EBRT) with a median dose of 5,040 cGy (range: 4,500~5,075 cGy) to the whole pelvis. Five patients with pathologically confirmed paraaortic lymph node metastasis received 4500 cGy to the paraaortic lymph nodes. Fifteen patients received low-dose intracavitary brachytherapy after their EBRT. A total dose of 7,500~9,540 cGy (median dose: 8511) was prescribed to the vaginal surface.

Results

Overall, 11 patients (13%) experienced disease relapse: 4 with initial stage I or II disease and 7 with initial stage III disease. Among the 54 stage I or II patients, 1 (2%) relapsed in the pelvis only, 2 (4%) relapsed in the vagina and distant organs, and 1 (2%) relapsed in the paraaortic lymph nodes (PANs). Among the 29 stage III patients, 1 (3%) relapsed in the vagina. The most common sites of failure for the stage III patients were the peritoneum (3 patients, 10%), PANs (2 patients, 7%), and lung (2 patients, 7%). With a median follow-up period of 86 months, the overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% for both. The five-year DFS rate was 93%, 100% and 74% for the stage I, II and III patients, respectively. Three patients experienced severe radiation-related late complications: RTOG (Radiation Therapy Oncology Group) grade 3 radiation cystitis was seen in one patient, and grade 3 bowel obstruction was seen in two patients.

Conclusions

Postoperative RT was useful for controlling pelvic disease. The major patterns of failure for stage III patients were peritoneal seeding and distant metastasis. Selective use of whole abdominal radiotherapy or adjuvant chemotherapy may improve the therapeutic outcome of these patients.

Citations

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Pattern of care and clinical outcome of patients with carcinoma endometrium and the impact of central histopathological review on management: A tertiary cancer centre experience
Rakhi Verma, Ajeet K. Gandhi, Madhup Rastogi, Vachaspati K. Mishra, Vikas Sharma, Akash Agarwal, Saumya Shukla, Rohini Khurana, Rahat Hadi, Anoop K. Srivastava, Nuzhat Husain
Journal of Cancer Research and Therapeutics.2024; 20(5): 1557. CrossRef
Does Prophylactic Paraortic Lymph Node Irradiation Improve Outcomes in Women With Stage IIIC1 Endometrial Carcinoma?
Jennifer Yoon, Halle Fitzgerald, Yaqun Wang, Qingyang Wang, Irina Vergalasova, Mohamed A. Elshaikh, Irina Dimitrova, Shari Damast, Jessie Y. Li, Emma C. Fields, Sushil Beriwal, Andrew Keller, Elizabeth A. Kidd, Melissa Usoz, Shruti Jolly, Elizabeth Jawors
Practical Radiation Oncology.2022; 12(2): e123. CrossRef
Efficacy of Para-Aortic Lymphadenectomy in Early-Stage Endometrioid Uterine Corpus Cancer
Seo-Yun Tong, Jong-Min Lee, Jae-Kwan Lee, Jae Weon Kim, Chi-Heum Cho, Seok-Mo Kim, Sang-Yoon Park, Chan-Yong Park, Ki-Tae Kim
Annals of Surgical Oncology.2011; 18(5): 1425. CrossRef
Current status in the management of uterine corpus cancer in Korea
Nan-Hee Jeong, Jong-Min Lee, Seon-Kyung Lee
Journal of Gynecologic Oncology.2010; 21(3): 151. CrossRef

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Occludin Expression in Brain Tumors and its Relevance to Peritumoral Edema and Survival: Min-Woo Park, Choong-Hyun Kim, Jin-Hwan Cheong, Koang-Hum Bak, Jae-Min Kim, Suck-Jun Oh; Cancer Res Treat. 2006;38(3):139-143. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.139

Abstract PDF PubReader ePub

Purpose

Peritumoral brain edema (PTBE) is a serious causative factor that contributes the morbidity or mortality of brain tumors. The development of PTBE is influenced by many factors, including such tight junction proteins as occludin. We evaluated the PTBE volume and survival time with respect to the occludin expression in various pathological types of brain tumors.

Materials and Methods

Fresh-frozen specimens from sixty patients who had brain tumors were obtained during surgery and the tumors were confirmed pathologically. The occludin expression was investigated by Western blot analysis. The PTBE volume was measured by using preoperative magnetic resonance (MR) imaging, and the survival time in each patient was estimated retrospectively.

Results

Occludin was detected in 41 (68.3%) of the cases with brain tumors and it was not expressed in the other 19 (31.7%) cases. Although the lowest expression was revealed in high-grade gliomas, its expression was variable according to the pathology of the brain tumors (p>0.05). The difference of PTBE volume between occludin-positive and negative brain tumors was statistically significant (2072.46±328.73 mm³ vs. 7452.42±1504.19 mm³, respectively, p=0.002). The mean survival time was longer in the occludin-positive tumor group than in the occludin-negative group (38.63±1.57 months vs. 26.16±3.83 months, respectively; p=0.016).

Conclusions

This study suggests that the occludin expression is highly correlated to the development of PTBE in brain tumors and it might be a prognostic indicator for patient survival.

Citations

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Tight junction proteins in glial tumors development and progression
Jakub Moskal, Slawomir Michalak
Frontiers in Cellular Neuroscience.2025;[Epub] CrossRef
Lipid-Based Nanocarriers for Neurological Disorders: A Review of the State-of-the-Art and Therapeutic Success to Date
Bwalya Angel Witika, Madan Sai Poka, Patrick Hulisani Demana, Scott Kaba Matafwali, Siyabonga Melamane, Sandile Maswazi Malungelo Khamanga, Pedzisai Anotida Makoni
Pharmaceutics.2022; 14(4): 836. CrossRef
Blood-Brain Barrier Alterations and Edema Formation in Different Brain Mass Lesions
Peter Solar, Michal Hendrych, Martin Barak, Hana Valekova, Marketa Hermanova, Radim Jancalek
Frontiers in Cellular Neuroscience.2022;[Epub] CrossRef
Evaluation of AQP4/TRPV4 Channel Co-expression, Microvessel Density, and its Association with Peritumoral Brain Edema in Intracranial Meningiomas
Konstantinos Faropoulos, Afroditi Polia, Chrisi Tsakona, Eleanna Pitaraki, Athanasia Moutafidi, George Gatzounis, Martha Assimakopoulou
Journal of Molecular Neuroscience.2021; 71(9): 1786. CrossRef
Peripheral Blood Occludin Level as a Biomarker for Perioperative Cerebral Edema in Patients with Brain Tumors
Shuhai Shi, Jingli Cheng, Chunyang Zhang, Tao Liang, Yunxin Zhang, Yongxing Sun, Ying Zhao, Weili Li, Baoguo Wang
Disease Markers.2020; 2020: 1. CrossRef
Intracerebral GM-CSF contributes to transendothelial monocyte migration in APP/PS1 Alzheimer’s disease mice
De S Shang, Yi M Yang, Hu Zhang, Li Tian, Jiu S Jiang, Yan B Dong, Ke Zhang, Bo Li, Wei D Zhao, Wen G Fang, Yu H Chen
Journal of Cerebral Blood Flow & Metabolism.2016; 36(11): 1978. CrossRef
Abnormal expression of an ADAR2 alternative splicing variant in gliomas downregulates adenosine-to-inosine RNA editing
Jun Wei, Zhaohui Li, Chao Du, Bin Qi, Xingli Zhao, Liping Wang, Lirong Bi, Guan Wang, Xuan Zhang, Xiaoyun Su, Yuzhuo Pan, Yu Tian
Acta Neurochirurgica.2014; 156(6): 1135. CrossRef
Evaluation of mast cells and hypoxia inducible factor-1 expression in meningiomas of various grades in correlation with peritumoral brain edema
Joanna Reszec, Adam Hermanowicz, Robert Rutkowski, Piotr Bernaczyk, Zenon Mariak, Lech Chyczewski
Journal of Neuro-Oncology.2013; 115(1): 119. CrossRef
Involvement of PI3K and ROCK signaling pathways in migration of bone marrow-derived mesenchymal stem cells through human brain microvascular endothelial cell monolayers
Mei-Na Lin, De-Shu Shang, Wei Sun, Bo Li, Xin Xu, Wen-Gang Fang, Wei-Dong Zhao, Liu Cao, Yu-Hua Chen
Brain Research.2013; 1513: 1. CrossRef

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AKAP12α is Associated with Promoter Methylation in Lung Cancer: Ukhyun Jo, Young Mi Whang, Han Kyeom Kim, Yeul Hong Kim; Cancer Res Treat. 2006;38(3):144-151. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.144

Abstract PDF PubReader ePub

Purpose

Promoter methylation is an important mechanism for silencing tumor-suppressor genes in cancer and it is a promising tool for the development of molecular biomarkers. The purpose of the present study was to investigate whether inactivation of the A Kinase Anchoring Protein 12 (AKAP12) gene is assoCiated with promoter methylation in lung cancer.

Materials and Methods

The AKAP12 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) in ten lung cancer cell lines. The methylation status of the AKAP12α promoter was analyzed by performing bisulfite sequencing analysis in ten lung cancer cell lines, twenty four lung tissues and matched normal tissues.

Results

The AKAP12α expression was reduced in 6 of 10 (60%) lung cancer cell lines, whereas the AKAP12β expression was absent in 1 of 10 (10%) lung cancer cell lines. The AKAP12α expression was restored after treatment with the demethylating agent 5-aza-2'-deoxycytidine in three lung cancer cell lines. Methylation of CpG island 1 in the AKAP12α promoter was detected in 30% of the lung cancer cell lines, whereas methylation of CpG island 2 in the AKAP12α promoter was observed in the immortalized bronchial cell line and in all the lung cancer cell lines. In lung tumors, the CpG island 1 in the AKAP12α promoter was infrequently methylated. However, CpG island 2 in the AKAP12α promoter was highly methylated in lung tumors compared with the surrounding normal tissues, and this was statistically significant (p=0.0001).

Conclusion

Our results suggest that inactivation of the AKAP12α expression is assoCiated with DNA methylation of the promoter region in lung cancer, and that AKAP12α may play an important role in lung cancer carcinogenesis.

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AKAP12 promotes cancer stem cell-like phenotypes and activates STAT3 in colorectal cancer
Ke Li, Xuan Wu, Yuan Li, Ting-Ting Hu, Weifeng Wang, Frank J. Gonzalez, Weiwei Liu
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Metastasis suppressor genes in clinical practice: are they druggable?
Irwin H. Gelman
Cancer and Metastasis Reviews.2023; 42(4): 1169. CrossRef
FGF10 Triggers De Novo Alveologenesis in a Bronchopulmonary Dysplasia Model: Impact on Resident Mesenchymal Niche Cells
Sara Taghizadeh, Cho-Ming Chao, Stefan Guenther, Lea Glaser, Luisa Gersmann, Gabriela Michel, Simone Kraut, Kerstin Goth, Janine Koepke, Monika Heiner, Ana Ivonne Vazquez-Armendariz, Susanne Herold, Christos Samakovlis, Norbert Weissmann, Francesca Ricci,
Stem Cells.2022; 40(6): 605. CrossRef
Identifying General Tumor and Specific Lung Cancer Biomarkers by Transcriptomic Analysis
Beatriz Andrea Otálora-Otálora, Daniel Alejandro Osuna-Garzón, Michael Steven Carvajal-Parra, Alejandra Cañas, Martín Montecino, Liliana López-Kleine, Adriana Rojas
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Gene expression changes in cervical squamous cancers following neoadjuvant interventional chemoembolization
Yonghua Chen, Yuanyuan Hou, Ying Yang, Meixia Pan, Jing Wang, Wenshuang Wang, Ying Zuo, Jianglin Cong, Xiaojie Wang, Nan Mu, Chenglin Zhang, Benjiao Gong, Jianqing Hou, Shaoguang Wang, Liping Xu
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The role of A-kinase anchoring proteins in cancer development
Erica Reggi, Dario Diviani
Cellular Signalling.2017; 40: 143. CrossRef
Elevated AKAP12 in Paclitaxel-Resistant Serous Ovarian Cancer Cells Is Prognostic and Predictive of Poor Survival in Patients
Nicholas W. Bateman, Elizabeth Jaworski, Wei Ao, Guisong Wang, Tracy Litzi, Elizabeth Dubil, Charlotte Marcus, Kelly A. Conrads, Pang-ning Teng, Brian L. Hood, Neil T. Phippen, Lisa A. Vasicek, William P. McGuire, Keren Paz, David Sidransky, Chad A. Hamil
Journal of Proteome Research.2015; 14(4): 1900. CrossRef
Suppression of tumor and metastasis progression through the scaffolding functions of SSeCKS/Gravin/AKAP12
Irwin H. Gelman
Cancer and Metastasis Reviews.2012; 31(3-4): 493. CrossRef
CancerMA: a web-based tool for automatic meta-analysis of public cancer microarray data
Julia Feichtinger, Ramsay J. McFarlane, Lee D. Larcombe
Database.2012;[Epub] CrossRef
The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells
Andrei Turtoi, Denis Mottet, Nicolas Matheus, Bruno Dumont, Paul Peixoto, Vincent Hennequière, Christophe Deroanne, Alain Colige, Edwin De Pauw, Akeila Bellahcène, Vincent Castronovo
Angiogenesis.2012; 15(4): 543. CrossRef
Mitochondrial Proteomic Analysis of Cisplatin Resistance in Ovarian Cancer
Nicole P. Chappell, Pang-ning Teng, Brian L. Hood, Guisong Wang, Kathleen M. Darcy, Chad A. Hamilton, G. Larry Maxwell, Thomas P. Conrads
Journal of Proteome Research.2012; 11(9): 4605. CrossRef
Akap12
Irwin Gelman
AfCS-Nature Molecule Pages.2011;[Epub] CrossRef
Retinoid-Induced Expression and Activity of an Immediate Early Tumor Suppressor Gene in Vascular Smooth Muscle Cells
Jeffrey W. Streb, Xiaochun Long, Ting-Hein Lee, Qiang Sun, Chad M. Kitchen, Mary A. Georger, Orazio J. Slivano, William S. Blaner, Daniel W. Carr, Irwin H. Gelman, Joseph M. Miano, Gian Paolo Fadini
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Inhibition of Phorbol Ester-induced Mouse Skin Tumor Promotion and COX-2 Expression by Celecoxib: C/EBP as a Potential Molecular Target: Kyung-Soo Chun, Joydeb Kumar Kundu, Kwang-Kyun Park, Won-Yoon Chung, Young-Joon Surh; Cancer Res Treat. 2006;38(3):152-158. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.1.152

Abstract PDF PubReader ePub

Purpose

Inflammation acts as a driving force for the development of cancer. Multiple lines of evidence suggest that nonsteroidal anti-inflammatory drugs, especially those that specifically target cyclooxygenase-2 (COX-2), are effective in preventing certain cancers. The present study was aimed at investigating the antitumor promoting potential of celecoxib in chemically induced mouse skin tumorigenesis, as well as elucidating the underlying molecular mechanisms.

Materials and Methods

To study the antitumor promoting effects of celecoxib, we used the classical two-stage mouse skin tumorigenesis model that involves initiation with a single application of 7,12-dimethylbenz [α]anthracene (DMBA) followed by promotion with repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of celecoxib on the expression of COX-2, vascular endothelial growth factor (VEGF), p65 and the different isoforms of CCAAT/enhancer binding protein (C/EBP) were examined by performing Western blot analysis. Electrophoretic mobility gel shift assay was used to examine the effects of celecoxib on the TPA-induced DNA binding activities of various transcription factors.

Results

Our study revealed that topical application of celecoxib (10µmol) significantly reduced the multiplicity of papillomas in DMBA-initiated and TPA-promoted mouse skin. Pretreatment with celecoxib also diminished the expression of COX-2 and VEGF in the mouse skin papillomas. Pretreatment with celecoxib attenuated DNA binding of transcription factor (C/EBP) in the TPA-stimulated mouse skin. Moreover, celecoxib suppressed the TPA-induced nuclear expression of C/EBPδ, but not C/EBPβ, in mouse skin in vivo.

Conclusion

Our study demonstrates the inhibitory effects of celecoxib on mouse skin tumor promotion, which was associated with a decreased expression of COX-2 and VEGF, as well as inhibition of C/EBP activation.

Citations

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Molecular Research on Oral Diseases and Related Biomaterials: A Journey from Oral Cell Models to Advanced Regenerative Perspectives
Thorsten Steinberg, Martin Philipp Dieterle, Pascal Tomakidi
International Journal of Molecular Sciences.2022; 23(9): 5288. CrossRef
Photobiomodulation therapy reduces acute pain and inflammation in mice
Glauce Regina Pigatto, Carolina Seabra Silva, Nivaldo Antonio Parizotto
Journal of Photochemistry and Photobiology B: Biology.2019; 196: 111513. CrossRef
Piceatannol inhibits phorbol ester-induced expression of COX-2 and iNOS in HR-1 hairless mouse skin by blocking the activation of NF-κB and AP-1
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COX‐2 inhibition prevents the appearance of cutaneous squamous cell carcinomas accelerated by BRAF inhibitors
Helena Escuin-Ordinas, Mohammad Atefi, Yong Fu, Ashley Cass, Charles Ng, Rong Rong Huang, Sharona Yashar, Begonya Comin-Anduix, Earl Avramis, Alistair J. Cochran, Richard Marais, Roger S. Lo, Thomas G. Graeber, Harvey R. Herschman, Antoni Ribas
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Targeted Deletion and Lipidomic Analysis Identify Epithelial Cell COX-2 as a Major Driver of Chemically Induced Skin Cancer
Jing Jiao, Tomo-O Ishikawa, Darren S. Dumlao, Paul C. Norris, Clara E. Magyar, Carol Mikulec, Art Catapang, Edward A. Dennis, Susan M. Fischer, Harvey R. Herschman
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Wen-Jane Lee, Keng-Hsin Lan, Chiang-Ting Chou, Yu-Chiao Yi, Wei-Chih Chen, Hung-Chuan Pan, Yen-Chun Peng, Keh-Bin Wang, Yi-Ching Chen, Te-Hsin Chao, Hsing-Ru Tien, Wayne Huey Herng Sheu, Meei-Ling Sheu
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Genetic ablation of cyclooxygenase-2 in keratinocytes produces a cell-autonomous defect in tumor formation
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Protective effect of baicalin against multiple ultraviolet b exposure-mediated injuries in C57BL/6 mouse skin
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Archives of Pharmacal Research.2011; 34(2): 261. CrossRef

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The Synergism between Belotecan and Cisplatin in Gastric Cancer: Joo Young Jung, Sang Hyun Song, Tae-Young Kim, Jung Hyun Park, Hyun-Soon Jong, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, Noe Kyoung Kim; Cancer Res Treat. 2006;38(3):159-167. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.159

Abstract PDF PubReader ePub

Purpose

We wanted to demonstrate the anti-cancer effect and interaction between belotecan and cisplatin on gastric cancer cell line and we evaluated the mechanisms of this synergistic effect in vitro.

Materials and Methods

The growth inhibitory effect of belotocan and cisplatin against several gastric cancer cell lines (SNU-5, SNU-16 and SNU-601) was estimated by tetrazolium dye assay. The effect of a combination treatment was evaluated by the isobologram method. The biochemical mechanisms for the interaction between the drugs were analyzed by measuring the formation of DNA interstrand cross-links (ICLs) and DNA topo-I activity.

Results

Belotecan showed synergism with cisplatin for growth inhibitory effect on the gastric cancer cell lines SNU-5, and SNU-16, but this was subadditive on the SNU-601 cell line. The formation of DNA ICLs in SNU-16 cells by cisplatin was increased by combination with belotecan, but this was not affected in SNU-601 cells. The topo-I inhibition by belotecan was enhanced at high concentrations of cisplatin in SNU-16, but not in SNU-601 cells.

Conclusion

Belotecan and cisplatin show various combination effect against gastric cancer cells. The synergism between cisplatin and belotecan could be the result of one of the following mechanisms: the modulating effect of belotecan on the repair of cisplatin-induced DNA adducts and the enhancing effect of cisplatin on the belotecan-induced topo-I inhibitory effect.

Citations

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Drug combinations of camptothecin derivatives promote the antitumor properties
Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef
The Advancement of Biodegradable Polyesters as Delivery Systems for Camptothecin and Its Analogues—A Status Report
Katarzyna Strzelecka, Urszula Piotrowska, Marcin Sobczak, Ewa Oledzka
International Journal of Molecular Sciences.2023; 24(2): 1053. CrossRef
Safe approaches for camptothecin delivery: Structural analogues and nanomedicines
Pablo Botella, Eva Rivero-Buceta
Journal of Controlled Release.2017; 247: 28. CrossRef
Sageone, a diterpene from Rosmarinus officinalis, synergizes with cisplatin cytotoxicity in SNU-1 human gastric cancer cells
Sabina Shrestha, Yeon Woo Song, Hyeonji Kim, Dong Sun Lee, Somi Kim Cho
Phytomedicine.2016; 23(13): 1671. CrossRef
Synthesis, characterisation, in vitro DNA binding properties and antioxidant activities of Ln(III) complexes with chromone-3-carbaldehyde-(2′-hydroxy) benzoyl hydrazone
Yong Li, Zheng-yin Yang, Tian-rong Li
Progress in Reaction Kinetics and Mechanism.2015; 40(4): 313. CrossRef
Combination therapy of cilengitide with belotecan against experimental glioblastoma
Young‐Hoon Kim, Jin Kyung Lee, Bokyong Kim, Judy Park DeWitt, Jung Eun Lee, Jung Ho Han, Seung‐Ki Kim, Chang Wan Oh, Chae‐Yong Kim
International Journal of Cancer.2013; 133(3): 749. CrossRef
Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model
Chae-Yong Kim, Su-Jung Lee, Seung-Ki Kim, Chul-Kee Park, Kyu-Chang Wang, Byung-Kyu Cho
Journal of Clinical Neuroscience.2012; 19(2): 301. CrossRef
Phase II study of combined belotecan and cisplatin as first-line chemotherapy in patients with extensive disease of small cell lung cancer
Junshik Hong, Minkyu Jung, Yu Jin Kim, Sun Jin Sym, Sun Young Kyung, Jinny Park, Sang Pyo Lee, Jeong Woong Park, Eun Kyung Cho, Sung Hwan Jeong, Dong Bok Shin, Jae Hoon Lee
Cancer Chemotherapy and Pharmacology.2012; 69(1): 215. CrossRef

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Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells: Yong-Seok Lee, Su-Mi Bae, Sun-Young Kwak, Dong-Chun Park, Yong-Wook Kim, Soo-Young Hur, Eun-Kyung Park, Byoung-Don Han, Young-Joo Lee, Chong-Kook Kim, Do Kang Kim, Woong-Shick Ahn; Cancer Res Treat. 2006;38(3):168-177. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.168

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Purpose

The tumor suppressor gene, p53, has been established as an essential component for the suppression of tumor cell growth. In this study, we investigated the time-course anticancer effects of adenoviral p53 (Adp53) infection on human ovarian cancer cells to provide insight into the molecular-level understanding of the growth suppression mechanisms involved in Adp53-mediated apoptosis and cell cycle arrest.

Materials and Methods

Three human cervical cancer cell lines (SiHa, CaSki, HeLa and HT3) were used. The effect of Adp53 infection was studied via cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay.

Results

Adp53 exerts a significant role in suppressing cervical cancer cell growth. Adp53 also showed growth inhibitory effects in each cell line, and it induced apoptosis and cell cycle arrest. Adp53 differentially regulated the expression of genes and proteins, and the gene expression profiles in the SiHa cells revealed that the p21, p53 and mdm2 expres sions were significantly up-regulated at 24 and 48 hr. Western blot shows that the p21 and p53 expression-levels were significantly increased after Adp53 infection. In addition, in all cell lines, both the CDK4 and PCNA protein expression levels were decreased 48 h after Adp53 infection. Cell cycle arrest at the G1 phase was induced only in the SiHa and HeLa cells, suggesting that exogenous infection of Adp53 in cancer cells was significantly different from the other HPV-associated cervical cancer cells.

Conclusion

Adp53 can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest, as well as through the regulation of the cell cycle-related proteins. The Adp53-mediated apoptosis can be employed as an advanced strategy for developing preferential tumor cell-specific delivery.

Citations

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Health‐promoting bioactivity and in vivo genotoxicity evaluation of a hemiepiphyte fig, Ficus dubia
Uthaiwan Suttisansanee, Pornsiri Pitchakarn, Pisamai Ting, Woorawee Inthachat, Parunya Thiyajai, Daraphan Rodthayoy, Jirarat Karinchai, Bhanumas Chantarasuwan, Onanong Nuchuchua, Piya Temviriyanukul
Food Science & Nutrition.2021; 9(4): 2269. CrossRef
Comprehensive Data of P53 R282 Gene Mutation with Human Papillomaviruses (HPV)-Associated Oral Squamous Cell Carcinoma (OSCC)
Tipaya Ekalaksananan, Weerayut Wongjampa, Pensiri Phusingha, Jureeporn Chuerduangphui, Patravoot Vatanasapt, Supannee Promthet, Natcha Patarapadungkit, Chamsai Pientong
Pathology & Oncology Research.2020; 26(2): 1191. CrossRef
Etoposide radiosensitizes p53-defective cholangiocarcinoma cell lines independent of their G2 checkpoint efficacies
Arunee Hematulin, Sutiwan Meethang, Kitsana Utapom, Sopit Wongkham, Daniel Sagan
Oncology Letters.2018;[Epub] CrossRef
Effect and Safety of Recombinant Adenovirus-p53 Transfer Combined with Radiotherapy on Long-Term Survival of Locally Advanced Cervical Cancer
Xing Su, Wen-juan Chen, Shao-wen Xiao, Xiao-fan Li, Gang Xu, Jian-ji Pan, Shan-wen Zhang
Human Gene Therapy.2016; 27(12): 1008. CrossRef
Celecoxib, a COX-2 Selective Inhibitor, Induces Cell Cycle Arrest at the G2/M Phase in HeLa Cervical Cancer Cells
Agustina Setiawati
Asian Pacific Journal of Cancer Prevention.2016; 17(4): 1655. CrossRef
Cisplatin sensitivity and mechanisms of anti-HPV16 E6-ribozyme on cervical carcinoma CaSKi cell line
Zhiguo Rao, Jianfei Gao, Bicheng Zhang, Bo Yang, Jiren Zhang
The Chinese-German Journal of Clinical Oncology.2012; 11(4): 237. CrossRef

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Case Reports

Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors of the Stomach: Report of Three Cases: Ji Seon Oh, Jae-Lyun Lee, Mi-Jung Kim, Min-Hee Ryu, Heung Moon Chang, Tae Won Kim, Se Jin Jang, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Yoon-Koo Kang; Cancer Res Treat. 2006;38(3):178-183. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.178

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Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.

Citations

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Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor
Dong-Hoe Koo, Min-Hee Ryu, Kyoung-Mee Kim, Han-Kwang Yang, Akira Sawaki, Seiichi Hirota, Jie Zheng, Bo Zhang, Chin-Yuan Tzen, Chun-Nan Yeh, Toshirou Nishida, Lin Shen, Li-Tzong Chen, Yoon-Koo Kang
Cancer Research and Treatment.2016; 48(4): 1155. CrossRef
Correlation between Computed Tomography and Pathological Findings of Gastrointestinal Stromal Tumors Treated with Imatinib Mesylate
Ki Choon Sim, Beom Jin Park, Na Yeon Han, Deuk Jae Sung, Min Ju Kim, Sung Bum Cho, Hyun Kwon Ha, Hyoung Rae Kim
Journal of the Korean Society of Radiology.2014; 71(5): 239. CrossRef
Diagnosis and Treatment of Gastrointestinal Stromal Tumor
Yoon-Koo Kang, Dong Hoe Koo
Korean Journal of Medicine.2013; 85(4): 341. CrossRef
Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang, Hye Jin Kang, Kyoung-Mee Kim, Taesung Sohn, Dongil Choi, Min-Hee Ryu, Woo Ho Kim, Han-Kwang Yang
Cancer Research and Treatment.2012; 44(2): 85. CrossRef
Efficacy of Imatinib Mesylate Neoadjuvant Treatment for a Locally Advanced Rectal Gastrointestinal Stromal Tumor
Kyu Jong Yoon, Nam Kyu Kim, Kang Young Lee, Byung Soh Min, Hyuk Hur, Jeonghyun Kang, Sarah Lee
Journal of the Korean Society of Coloproctology.2011; 27(3): 147. CrossRef
Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang, Kyoung-Mee Kim, Taesung Sohn, Dongil Choi, Hye Jin Kang, Min-Hee Ryu, Woo Ho Kim, Han-Kwang Yang
Journal of Korean Medical Science.2010; 25(11): 1543. CrossRef
Clinical Practice Guideline for Adequate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang
Journal of the Korean Medical Association.2007; 50(9): 830. CrossRef

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Long-term Survival after Surgical Resection for Liver Metastasis from Gastric Cancer: Two Case Reports: Jong Keun Lim, Joong Bae Ahn, Sung Ha Cheon, Hyun Chang, Jong Yul Jung, Sun Young Rha, Jae Kyung Roh, Sung Hoon Noh, Ho Geun Kim, Hyun Cheol Chung, Hei-Cheul Jeung; Cancer Res Treat. 2006;38(3):184-188. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.184

Abstract PDF PubReader ePub

Surgical resection of colorectal cancer metastasis to the liver results in a 5-year survival rate of around 40%. Liver metastasis from other cancers such as neuroendocrine carcinoma and genitourinary tumors are also treated effectively with combined liver resection. However, hepatic metastasectomy for liver tumor from gastric cancer hasn't been considered as a standard treatment, and the benefit for this treatment has not been established. We report here on two cases of gastrectomy and combined liver resection for synchronous liver metastasis without any evidence of other metastatic lesions, and these two patients have survived for more than 7 years without evidence of disease recurrence. In conclusion, for patients with hepatic metastasis from gastric cancer, combined surgical resection of the liver metastasis should be considered as a treatment option when metastasis to other sites can be excluded.

Citations

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Radical gastrectomy with hepatoarterial catheter implantation for late-stage gastric cancer
Guo-Liang Yao
World Journal of Gastroenterology.2015; 21(9): 2754. CrossRef

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